New Treatment Strategies for Extended-spectrum beta-lactamase-producing Enterobacteriaceae

Extended-spectrum beta-lactamases (ESBLs) are a major public health concern. The current standard of therapy for ESBL-producing Enterobacteriaceae is a carbapenem. However, the increasing rates of carbapenem resistance necessitate a more judicious approach to its use. A decrease of the consumption of carbapenems is advocated. In addition, there is an increasing interest in potential alternatives to these drugs. In 2011, the Comite de l'antibiogramme de la Societe francaise de microbiologie (CASFM) recommended to stop the interpretive lecture of susceptibility to cephalosporins and beta-lactam/beta-lactamase inhibitor combinations (BL/BLIs) for ESBL-producing Enterobacteriaceae. Breakpoints of these antibiotics have been lowered, allowing them to be considered as a therapeutic option. With the revised breakpoints (1-2 mg/l), one third of ESBL-producing Enterobacteriaceae are classified as susceptible. Several studies reported a successful treatment of infections caused by ESBL-producing organisms with extended-spectrum cephalosporins (ESC) or BL/BLIs, especially in bacteraemia or urinary tract infections. However, these studies were retrospective. Prospective clinical trials are urgently needed to validate this result, especially in infections due to ESBL-producing organisms. Minimum inhibitory concentrations, inoculum effect, the type and the severity of infections were major predictive factors of outcome. Cephamycyin (cefoxitin) or temocillin could also be a useful carbapenem-sparing agent. Despite all these therapeutic options being viable, new agents are still needed. Avibactam, a novel beta-lactamase inhibitor which is associated with ESC, demonstrates potent activity against ESBL-producing Enterobacteriaceae. Future antibiotics are promising and are referenced in this review.